Transition metal-catalyzed coupling reaction of aryl halides with suitable nucleophiles, such as organic amines, active methylene compounds, alkynes, phenols, alcohols, thiophenols, sodium sulfinates, sodium sulfide, or phosphates is an effective method to form C—N, C—C, C—O, C—S, and C—P bonds. Generally, aryl iodide and aryl bromide are of higher reactivity, thus can achieve the corresponding coupling reaction when catalyzed by transition metals such as palladium, copper, nickel, etc. Compared with bromine (iodo) aromatic hydrocarbon, chlorination aromatic hydrocarbons are cheaper and of better application prospect, however, C—Cl bond is of high energy (Grushin, V V; Alper, H. Chem. Rev. 1994, 94, 1047.), which makes it difficult for the oxidative addition between C—Cl bond and transition metals. The reaction is not as efficient as the bromide and iodine. The C—N coupling reaction of aryl chlorides catalyzed by palladium and nickel has been reported. The use of large sterically hindered phosphorus ligands to promote the reaction is an effective strategy. In 2005, Hartwig's group has used large steric phosphines with ferrocene structure to successfully complete the coupling reaction of chlorinated aromatic ring or aromatic heterocyclic compound with the primary amine, in which the equivalent of the catalyst and the ligand in the system can be reduced even to one hundred thousandth molar equivalent. For certain aromatic heterocyclic ring substrates, this type of reaction can be achieved at room temperature, which fully demonstrates the high efficiency of the catalyst system. Moreover, the reaction is also compatible with the substituent groups on the benzene ring (Shen, Q.; Shekhar, S Stambuli, J P; Hartwig, J F Angew. Chem. Int. Ed. 2005, 44, 1371.1.

In 2011, Buchwald's team found that chlorinated aromatics can be coupled to primary amines and secondary amines, respectively by employing different phosphine ligands. The system has broad compatibility with substrates. Besides general aliphatic amines, the heterocyclic aromatic amine can also be subjected to the coupling reaction successfully (Maiti, D.; Fors, B P; Henderson, J L; Nakamura, Y.; Buchwald, S L Chem. Sci. 2011, 2, 57.).

Although palladium and nickel are highly efficient in catalyzing the amination reaction of chlorinated aromatic hydrocarbons, there still are some problems in large-scale applications: 1. in the system, the addition of large sterically hindered, complex phosphine ligands or azacarbene ligands is necessary to promote the reaction; 2. the palladium catalyst is expensive, and the reaction operation required for zero-valent nickel is quite demanding, which to some extent has limited the application thereof. Compared with the above, copper catalysts are inexpensive, stable, and readily available, and the ligands used are in simple structure, which obviously avoids those deficiencies. However, the copper-catalyzed coupling reaction substrates reported so far are mostly limited to iodinated and brominated substrates.
In 2007, Pellón's group has achieved the coupling reaction of aliphatic amine with 2-chlorobenzoic acid under the action of ultrasound by and the promoting effects of the ortho-carboxy group of 2-chlorobenzoic acid, and good yield can be obtained for both primary amine and the secondary amine. However, this method is only effective for ortho-carboxy substituted substrates, which cannot be generally applied (Docampo, M L; Pellón, R F; Estevez-Braun, A.; Ravelo, A G Eur. J. Org. Chem. 2007, 4111). This reaction is essentially a nucleophilic substitution reaction rather than a coupling reaction, and the reaction temperature is very high.

Another report on the Ullmann coupling reaction of chlorinated aromatic hydrocarbons was reported by Taillefer's group. They used 2,2,6,6-tetramethyl-3,5-heptanedione as ligand to achieve the C—O coupling of chlorobenzene and phenols. The major disadvantage of this system is that up to 0.8 equivalents of ligand should be added into the reaction, thus reducing the economical efficiency of the reaction (Xia, N.; Taillefer, M. Chem. Eur. J. 2008, 14, 6037.).

In 2012, Ma Dawei's group has used the oxalic acid 2,6-dimethylphenyl monoamide carboxylic acid as a ligand for copper-catalyzed C—N coupling reaction of aryl iodide or bromine with organic amine (Org. Lett 2012, 14, 3056-3059). Recently, they have successfully applied oxalic diamide ligands designed based on that in the coupling reaction of aryl chlorides, and found that various types of nucleophiles can be used in the reaction, including primary amines, cyclic secondary amines, ammonium hydroxide, phenol, etc. This reaction provides coupled products in a good yield (J. Am. Chem. Soc. 2015, 137, 11942-11945; Org. Lett. 2015, 17, 5934-5937.).
In summary, the copper-catalyzed coupling reaction of aryl chlorides has very important application prospects, and suitable ligands are the key to such reactions. There is still a lack of a catalytic system for copper-catalyzed aryl chloride coupling reactions that is simple to be prepared, suitable for industrial applications that enables efficient reaction.